methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate → (S)-2-(Tert-butoxycarbonylamino)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl]propanoic acid

HRID 215938노트

반응식

HRID 215938 반응식
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([B:21]2[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]2)=[CH:17][CH:16]=1)[C:10]([O:12]C)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].B(C1C=CC(C[C@H](NC(OC(C)(C)C)=O)C(O)=O)=CC=1)(O)O>>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:16]=[CH:17][C:18]([B:21]2[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]2)=[CH:19][CH:20]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

3

반응물 2

HCID 10949509methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoateHCID 58746869[(S)-3-(4-boronophenyl)-2-((tertbutoxycarbonyl)amino)propanoic acid]

생성물 1

HCID 10644158(S)-2-(Tert-butoxycarbonylamino)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl]propanoic acid

실험 절차

The above organic layer of the ester was stirred with aqueous lithium hydroxide solution (23 g in 500 mL water) at room temperature for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 mL). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 mL, additional water was added during distillation). The slurry was filtered through a pad of cellulose and washed with water (200 mL). The filtrate was washed with MTBE (500 mL) and rediluted with 700 mL MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 mL) and concentrated under reduced pressure to the acid compound as a brown oil (206 g, 95% yield based on estimated purity by NMR). The crude product can be used directly in the following step. Alternatively, the compound can be purified by crystallization from MTBE/heptane to give a white solid, which contains a small amount of the corresponding boronic acid, (S)-3-(4-boronophenyl)-2-(tert-butoxycarbonylamino)propanoic acid. MS (ESI): MH+=392.2, MNH4+=409.2, M2H+=783.4, M2NH4+=800.4. 1H NMR (CDCl3) δ 7.95 (br s, 1H), 7.76 (d, J=7.8 Hz, 2H), 7.21 (d, J=7.6 Hz, 2H), 5.03 (d, J=7.8 Hz, 1H), 4.62 (m, 1H), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.

후처리

  1. customAlternatively, the compound can be purified by crystallization from MTBE/heptane
  2. customto give a white solid, which

출처 및 근거

ORD 기록
ord-bd986a8bfe46489bbb7e76e21c5cfd27
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193204B2

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